Dimethylamine → HCID 22506064, compound

HRID 1385604Notes

Reaction equation

HRID 1385604 reaction equation
[S:1]1(=[O:13])(=[O:12])[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:14][NH:15][CH3:16]>>[CH3:14][N:15]([CH3:16])[C:10]1[CH:9]=[CH:8][C:7]2[S:1](=[O:12])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][C:6]=2[CH:11]=1

Participants

3

Reactant 2

HCID 674Dimethylamine2×HCID 2202512,3,4,5-tetrahydro-1-benzothiepine 1,1-dioxide

Product 1

HCID 22506064HCID 22506064, compoundYield 90.5%

Conditions

Temperature
110 °C

Procedure

To a solution of 13.00 g (28.98 mmol) of enantiomerically-enriched tetrahydrobenzothiepine-1,1-dioxide (obtained from Step 8) in 73 mL of dimethylamine (2.0 M in THF, 146 mmol) in a Parr Reactor was added about 20 mL of neat dimethylamine. The mixture was sealed and stirred at 110° C. overnight, and cooled to ambient temperature. The excess dimethylamine was evaporated. The crude oil was dissolved in 200 mL of ethyl acetate and washed with 100 mL of water, dried over MgSO4 and concentrated in vacuo. Purification on a silica gel column (Waters Prep 500) using 20% ethyl acetate/hexane gave 12.43 g (90.5%) of the enantiomerically-enriched 7-(dimethylamino)tetrahydrobenzothiepine-1,1-dioxide (4R,5R) as a colorless solid: 1H NMR (CDCl3) δ0.87-0.93 (m, 6H), 1.10-1.68 (m, 12H), 2.17-2.25 (m, 1H), 2.81 (s, 6H), 2.99 (d, J=15.3 Hz, 1H), 3.15 (d, J=15.3 Hz, 1H), 3.84 (s, 3H), 4.11 (d, J=7.5 Hz, 1H), 5.49 (s, 1H), 5.99 (d, J=2.4 Hz, 1H), 6.51 (dd, J=8.7 Hz, 2.4 Hz, 1H), 6.94 (d, J=8.7 Hz, 2H), 7.42 (d, J=8.4 Hz, 2H), 7.90 (d, J=8.7 Hz, 1H). The product was determined to have 78% e.e. by chiral HPLC on a Chiralpak AD column using 5% ethanol/hexane as the eluent. Recrystallization of this solid from ethyl acetate/hexane gave 1.70 g of the racemic product. The remaining solution was concentrated and recrystallized to give 9.8 g of colorless solid. Enantiomeric excess of this solid was determined by chiral HPLC on a Chiralpak AD column using 5% ethanol/hexane as the eluent. It showed to have 96% e.e with the first eluting peak as the major product.

Workup

  1. customThe mixture was sealed
  2. temperaturecooled to ambient temperature
  3. customThe excess dimethylamine was evaporated
  4. dissolutionThe crude oil was dissolved in 200 mL of ethyl acetate
  5. washwashed with 100 mL of water
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customPurification on a silica gel column (Waters Prep 500)

Sources & evidence

ORD record
ord-fb49ddde06424560acb9d14db0aaf05e
Source dataset
uspto-grants-2001_07
Patent number
US06262277B1

Reaction notes

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